Bisoprolol Versus Celiprolol on Dynamic Hyperinflation, Cardiopulmonary Exercise and Domiciliary Safety in Copd: a Single Centre, Randomised, Crossover Study

TY - JOUR

T1 - Bisoprolol Versus Celiprolol on Dynamic Hyperinflation, Cardiopulmonary Exercise and Domiciliary Safety in Copd

T2 - a Single Centre, Randomised, Crossover Study

AU - Anderson, William J.

AU - Short, Philip

AU - Ross, Rose

AU - Lipworth, Brian J.

N1 - Funding Information: This study received financial grant support from the TENOVUS Scotland charity, reference number 218.804866. Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC.

PY - 2023/7/14

Y1 - 2023/7/14

N2 - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequently associated with cardiovascular disease. The utility of beta-blockers for treating patients with COPD may be beneficial, but their safety remains uncertain, including worsening of dynamic hyperinflation (DH) during exercise. We hypothesised that among cardioselective beta-blockers celiprolol, due to its partial beta-2 agonist activity, may be safer than bisoprolol on exercise DH. METHODS: We measured isotime inspiratory capacity (IC) during cycle endurance testing in eleven moderate-severe COPD subjects, alongside other non-invasive cardiopulmonary exercise, bioreactance cardiac output, pulmonary function, biomarkers and daily domiciliary measures. Participants received titrated doses of either bisoprolol (maximim 5 mg) or celiprolol (maximum 400 mg) in randomised crossover fashion, each over 4 weeks. RESULTS: Clinically relevant DH occurred between resting and exercise isotime IC but showed no significant difference with either beta-blocker compared with post-run-in pooled baseline or between treatments. There were no other significant differences observed for remaining exercise ventilatory; non-invasive cardiac output; resting pulmonary function; beta-2 receptor and cardiac biomarkers; domiciliary pulmonary function, oxygen saturation and symptom outcomes, either between treatments or compared with baseline. No significant adverse effects occurred. CONCLUSIONS: Significant DH in moderate-severe COPD subjects was no different between bisoprolol or celiprolol or versus baseline. A broad spectrum of other non-invasive cardiopulmonary and domiciliary safety outcomes was equally reassuring. Bronchoprotection with a concomitant long-acting muscarinic antagonist might be an important safety measure in this context. TRIAL REGISTRATION NUMBER: NCT02380053.

AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequently associated with cardiovascular disease. The utility of beta-blockers for treating patients with COPD may be beneficial, but their safety remains uncertain, including worsening of dynamic hyperinflation (DH) during exercise. We hypothesised that among cardioselective beta-blockers celiprolol, due to its partial beta-2 agonist activity, may be safer than bisoprolol on exercise DH. METHODS: We measured isotime inspiratory capacity (IC) during cycle endurance testing in eleven moderate-severe COPD subjects, alongside other non-invasive cardiopulmonary exercise, bioreactance cardiac output, pulmonary function, biomarkers and daily domiciliary measures. Participants received titrated doses of either bisoprolol (maximim 5 mg) or celiprolol (maximum 400 mg) in randomised crossover fashion, each over 4 weeks. RESULTS: Clinically relevant DH occurred between resting and exercise isotime IC but showed no significant difference with either beta-blocker compared with post-run-in pooled baseline or between treatments. There were no other significant differences observed for remaining exercise ventilatory; non-invasive cardiac output; resting pulmonary function; beta-2 receptor and cardiac biomarkers; domiciliary pulmonary function, oxygen saturation and symptom outcomes, either between treatments or compared with baseline. No significant adverse effects occurred. CONCLUSIONS: Significant DH in moderate-severe COPD subjects was no different between bisoprolol or celiprolol or versus baseline. A broad spectrum of other non-invasive cardiopulmonary and domiciliary safety outcomes was equally reassuring. Bronchoprotection with a concomitant long-acting muscarinic antagonist might be an important safety measure in this context. TRIAL REGISTRATION NUMBER: NCT02380053.

KW - COPD Pharmacology

KW - Exercise

KW - Pulmonary Disease, Chronic Obstructive

KW - Respiratory Measurement

KW - Pulmonary Disease

KW - Chronic Obstructive

UR - https://www.scopus.com/pages/publications/85164755760

U2 - 10.1136/bmjresp-2023-001670

DO - 10.1136/bmjresp-2023-001670

M3 - Article

C2 - 37451701

SN - 2052-4439

VL - 10

JO - BMJ Open Respiratory Research

JF - BMJ Open Respiratory Research

IS - 1

M1 - e001670

ER -